Abstracts

Rationale: GABA-B receptors play an important role among inhibitory systems especially at early developmental stages. Their effects are complicated by the fact that they are localized not only postsynaptically but also presynaptically as auto- as well as heteroreceptors. Therefore we studied possible anticonvulsant action of a potent GABA-B receptor agonist SKF97541 in a model of cortical epileptic afterdischarges at different levels of maturation.Methods: Male rats 12, 18 and 25 days old were implanted with cortical stimulation and registration electrodes. Fifteen-second stimulation series of 1-ms biphasic pulses at 8-Hz frequency were applied to sensorimotor cortex with intensity increasing from 0.2 to 15 mA. Two successive stimulations were separated by at least 10-min intervals. SKF97541 was administered intraperitoneally at doses from 0.1 to 1 mg/kg 15 min before the first stimulation. Thresholds for four different phenomena (movements elicited by stimulation, epileptic afterdischarges characterized by spike-and-wave rhythm in the EcoG, clonic seizures accompanying this type of afterdischarges, and transition into another, limbic type of afterdischarges accompanied by behavioral arrest and behavioral automatisms) were established and duration of epileptic afterdischarges was measured.Results: Threshold intensities for movements directly induced by stimulation were markedly increased by SKF97541 in all three age groups, this effect was less expressed in 25-day-old than in two younger groups. The same applied for thresholds for spike-and-wave type of afterdischarges and even more for accompanying clonic seizures so that spike-and-wave afterdischarges must not be accompanied by a motor component. On the contrary, transition into the limbic type of afterdischarges was not significantly influenced in the two younger groups (with an outlined tendency to a decrease in 18-day-old rats) but it was significantly decreased by the highest dose of SKF97541 in 25-day-old rats. Duration of afterdischarges was shortened in 12-day-old rats if low and medium intensities of current were used. In contrast, there was a dose-dependent prolongation of afterdischarges in 18- and 25-day-old animals partly due to an increased incidence of transition into limbic type of afterdischarges.Conclusions: Both anti- and proconvulsant effects of the GABA-B receptor agonist were found. Anticonvulsant effects were marked in 12-day-old rats and against motor phenomena, proconvulsant action was observed mostly in connection with the transition into the limbic type of afterdischarges. This study was supported by a grant No.305/05/2581 of the Grant Agency of the Czech Republic.